While they potentially offer many advantages due to their xe2x80x9corganic nature,xe2x80x9d conventional poly(xcex1-amino acids) possess many undesirable physical, chemical and biodegradation properties. For example, the biological and material properties of conventional poly(xcex1-amino acids) cannot be varied over a wide range. In addition, the synthesis of many conventional poly(xcex1-amino acids) is difficult and expensive.
A considerable amount of attention has therefore been focussed on replacing the amide (peptide) linkage in the conventional poly(xcex1-amino acids) with a variety of non-amide bond to provide novel polymeric systems that are based on xcex1-amino acids. One class of xcex1-amino acid derived polymers are polyisopeptides (alternatively known as pseudo-poly(amino acids)), which belong to the XY-type heterochain polymers. Polyisopeptides are usually foamed by linking trifunctional xcex1-amino acids in the backbone chains. However, relatively few attempts have been made to synthesize polyisopeptides. For example, Sekiguchi et al. obtained poly-xcex2-(xcex1-alkyl-L-aspartate) by the ring-opening polymerization of xcex2-lactams. See, Rodriguez-Galan, A. et al., Makromol. Chem., Makromol. Symp., 6, 277 (1986) and Vives, J. et al., Makromol. Chem., Rapid Commun., 10(1):13 (1989). One major limiting feature of polyisopeptides is that structural modifications are limited solely to chemical variations at the N-acyl residue of the polyisopeptide. This narrow range of chemical modification has resulted in an undesirably narrow range of material properties of these polymers.
Another class of xcex1-amino acid derived polymers are amino acid based bioanalagous polymers (AABBPs), which belong to the XX-YY heterochain polymers. AABBPs are mainly obtained by the polycondensation of XX (one type of monomer having two X functional groups) and YY (another type of monomer having two Y functional groups). AABBPs are not pure polyamino acids or pseudo-polyamino acids because they include residues of other types of monomers (e.g., dicarboxylic acids and diols).
One class of AABBPs are poly(ester ureas) (PEUs), which are prepared from bis-xcex1-aminoacyl diol monomers. The first attempt to use bis-xcex1-aminoacyl(phenylalanyl) diol for preparing bioabsorbable, semi-physiological polymers similar to poly(ester urea) was by Huang et al. Huang S. J., et al., J. Appl. Polym. Sci., 23(2): 429 (1979). Only low-molecular-weight PEUs, having limited material properties, could be prepared by this route.
Lipatova et al. have also synthesized semi-physiological poly(ester urethane ureas) from bis-L-phenylalanyl diols, diols, and diisocyanates. Lipatova T. E., et al., Dokl. Akad. Nauk SSSR, 251(2): 368 (1980) and Gladyr I. I., et al. Vysokomol. Soed., 31B(3): 196 (1989). However, no information on the synthesis of the starting material (e.g., xcex1-diamino diesters) was given.
Yoneyama et al. reported on the synthesis of high-molecular-weight semi-physiological PEUs by the interaction of free xcex1-diamino-diesters with non-physiological diisocyanates. Yoneyama M., et al., Polym. Prepr. Jpn., 43(1): 177 (1994). Contrary to Huang et al. (Huang S. J., et al., J. Appl. Polym. Sci., 23(2): 429 (1979)), high-molecular-weight PEUs were obtained in some cases. In view of this preliminary data, there remains an ongoing need for novel polymers based on xcex1-amino acids that possess a wide range of physical, chemical and biodegradation properties.
The present invention provides polymers that are based on xcex1-amino acids. In contrast to conventional poly(xcex1-amino acids), the polymers of the present invention (e.g., elastomeric functional copolyester amides and copolyester urethanes) possess advantageous physical, chemical and biodegradation properties. For example, the polymers of the present invention possess suitable biodegradation (weight loss percent) properties under varying conditions, (see, Table III). The hydrolysis of the polymers can be catalyzed by hydrolases (e.g., trypsin, xcex1-chymotrypsin, lipase, etc.). As such, the polymers can be used as carriers for covalent immobilization (attachment) of various drugs and other bioactive substances. In addition, the enzyme catalyzed biodegradation rates of the polymer of the present invention can be changed by varying the polymer composition (e.g., l/p ratio) and/or the nature of the functional groups (e.g., dicarboxylic acids, diols, or xcex1-amino acids).
The present invention provides a polymer of formula (VII): 
wherein
m is about 0.1 to about 0.9;
p is about 0.9 to about 0.1;
n is about 50 to about 150;
each R1 is independently (C2-C20)alkylene;
each R2 is independently hydrogen, or (C6-C10)aryl(C1-C6)alkyl;
each R3 is independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C6-C10)aryl(C1-C6)alkyl; and
each R4 is independently (C2-C20)alkylene; comprising one or more subunits of the formula (I): 
xe2x80x83and one or more subunits of the formula (II): 
xe2x80x83wherein
the combined number of subunits (I) and (II) is about 50 to about 150.
Specifically, each R1 can independently be (CH2)4, (CH2)8, or (CH2)12; R2 can independently be hydrogen or benzyl; each R3 can independently be iso-butyl or benzyl; and R4 can independently be (CH2)4, (CH2)6, (CH2)8, or (CH2)12.
The present invention also provides a polymer of formula (VII): 
wherein
m is about 0.1 to about 0.9;
p is about 0.9 to about 0.1;
n is about 50 to about 150;
each R1 is independently (C2-C20)alkylene;
each R2 is independently hydrogen, or (C6-C10)aryl(C1-C6)alkyl;
each R3 is independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C6-C10)aryl(C1-C6)alkyl; and
each R4 is independently (C2-C20)alkylene.
Specifically, each R1 can independently be (CH2)4, (CH2)8, or (CH2)12; each R2 can independently be hydrogen or benzyl; each R3 can independently be iso-butyl or benzyl; each R4 can independently be (CH2)4, (CH2)6, (CH2)8, or (CH2)12; p/(p+m) can be about 0.9 to about 0.1; and m/(p+m) can be about 0.1 to about 0.9.
The present invention also provides a polymer of formula (VII) formed from an amount of one or more compounds of formula (III): 
wherein
each R3 is independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C6-C10)aryl(C1-C6)alkyl; and
R4 is independently (C2-C20)alkylene; or a suitable salt thereof; and an amount of one or more compounds of formula (IV): 
xe2x80x83wherein
R2 is independently hydrogen, or (C6-C10)aryl(C1-C6)alkyl; or a suitable salt thereof; and
an amount of one or more compounds of formula (V): 
wherein
R1 is independently (C2-C20)alkylene; and
each R5 is independently (C6-C10)aryl, optionally substituted with one or more nitro, cyano, halo, trifluoromethyl, or trifluoromethoxy.
Specifically, R1 can independently be (CH2)4, (CH2)8, or (CH2)12; R2 can independently be hydrogen or benzyl; each R3 can independently be iso-butyl or benzyl; R4 can independently be (CH2)4, (CH2)6, (CH2)8, or (CH2)12; each R5 can independently be p-nitrophenyl; the compound of formula (III) can be the di-p-tolunesulfonic acid salt of a bis-(L-xcex1-amino acid)-xcex1,xcfx89-alkylene diester; the compound of formula (IV) can be the di-p-tolunesulfonic acid salt of L-lysine benzyl ester; and the compound of formula (V) can be di-p-nitrophenyl adipate, di-p-nitrophenyl sebacinate, or di-p-nitrophenyl dodecyldicarboxylate.
The present invention also provides a method for preparing a polymer of formula (VII): 
wherein
m is about 0.1 to about 0.9;
p is about 0.9 to about 0.1;
n is about 50 to about 150;
each R1 is independently (C2-C20)alkylene;
each R2 is independently hydrogen, or (C6-C10)aryl(C1-C6)alkyl;
each R3 is independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C6-C10)aryl(C1-C6)alkyl; and
each R4 is independently (C2-C20)alkylene; comprising contacting an amount of one or more compounds of formula (III): 
xe2x80x83or a suitable salt thereof; and
an amount of one or more compounds of formula (IV): 
or a suitable salt thereof; and
an amount of one or more compounds of formula (V): 
wherein
each R5 is independently (C6-C10)aryl optionally substituted with one or more nitro, cyano, halo, trifluoromethyl, or trifluoromethoxy;
under suitable conditions to provide the polymer of formula (VII).
Specifically, each R1 can independently be (CH2)4, (CH2)8, or (CH2)12; each R2 can independently be hydrogen or benzyl; each R3 can independently be iso-butyl or benzyl; each R4 can independently be (CH2)4, (CH2)6, (CH2)8, or (CH2)12; each R5 can be p-nitrophenyl; the compound of formula (III) can be the di-p-tolunesulfonic acid salt of a bis-(L-xcex1-amino acid)-xcex1,xcfx89-alkylene diester; the compound of formula (IV) can be the di-p-tolunesulfonic acid salt of L-lysine benzyl ester; the compound of formula (V) can be di-p-nitrophenyl adipate, di-p-nitrophenyl sebacinate, or di-p-nitrophenyl dodecyldicarboxylate; p/(p+m) can be about 0.9 to about 0.1; and m/(p+m) can be about 0.1 to about 0.9. The contacting can be carried out in the presence of a base, wherein the base can be triethylamine. The contacting can also be carried out in the present, of a solvent, wherein the solvent can be N,N-dimethylacetamide. The contacting can also be carried out at a temperature of about 50xc2x0 C. to about 100xc2x0 C. The contacting can preferably occur for about 10 hours to about 24 hours. The polymer of formula (VII) can also optionally be purified.
The present invention also provides a polymer of formula (XI): 
wherein
m is about 0.1 to about 0.9;
p is about 0.9 to about 0.1;
n is about 50 to about 150;
each R2 is independently hydrogen, or (C6-C10)aryl(C1-C6)alkyl;
each R3 is independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C6-C10)aryl(C1-C6)alkyl;
each R4 is independently (C2-C20)alkylene; and
each R6 is independently (C1-C20)alkylene or (C2-C8)alkyloxy(C2-C20)alkylene;
comprising one or more subunits of the formula (VIII): 
wherein
each R3 is independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C6-C10)aryl(C1-C6)alkyl; and
R4 is independently (C2-C20)alkylene;
R6 is independently (C2-C20)alkylene or (C2-C8)alkyloxy(C2-C20)alkylene; and
one or more subunits of the formula (IX): 
wherein
the total number of subunits (VIII) and (IV) is about 50 to about 150;
R2 is independently hydrogen, or (C6-C10)aryl(C1-C6)alkyl.
Specifically, R2 can independently be hydrogen or benzyl; each R3 can independently be iso-butyl or benzyl; R4 can independently be (CH2)4, (CH2)6, (CH2)8 or (CH2)12; and R6 can independently be (CH2)3 or (CH2)2xe2x80x94Oxe2x80x94(CH2)2.
The present invention also provides a polymer of formula (XI): 
wherein
m is about 0.1 to about 0.9;
p is about 0.9 to about 0.1;
n is about 50 to about 150;
each R2 is independently hydrogen, or (C6-C10)aryl(C1-C6)alkyl;
each R3 is independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C6-C10)aryl(C1-C6)alkyl;
each R4 is independently (C2-C20)alkylene; and
each R6 is independently (C2-C20)alkylene or (C2-C8)alkyloxy(C2-C20)alkylene.
Specifically, each R2 can independently be hydrogen or benzyl; each R3 can independently be iso-butyl or benzyl; each R4 can independently be (CH2)4, (CH2)6, (CH2)8, or (CH2)12; each R6 can independently be (CH2)3 or (CH2)2xe2x80x94Oxe2x80x94(CH2)2; p/(p+m) can be about 0.9 to about 0.1; and m/(p+m) can be about 0.1 to about 0.9.
The present invention also provides a polymer of formula (XI) formed from an amount of one or more compounds of formula (III): 
wherein each R3 is independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)alkynyl, or (C6-C10)aryl(C1-C6)alkyl; and
R4 is independently (C2-C20)alkylene; or a suitable salt thereof; and
an amount of one or more compounds of formula (IV): 
wherein
R2 is independently hydrogen, or (C6-C10)aryl(C1-C6)alkyl; or a suitable salt thereof, and
an amount of one or more compounds of formula (X): 
wherein
each R5 is independently (C1-C10)aryl optionally substituted with one or more nitro, cyano, halo, trifluoromethyl, or trifluoromethoxy; and
R6 is independently (C2-C20)alkylene or (C2-C8)alkyloxy(C2-C20)alkylene.
Specifically, R2 can independently be hydrogen or benzyl; each R3 can independently be iso-butyl or benzyl; R4 can independently be (CH2)4, (CH2)6, (CH2)8, or (CH2)12; each R5 can be p-nitrophenyl; R6 can independently be (CH2)3 or (CH2)2xe2x80x94Oxe2x80x94(CH2)2; the compound of formula (III) can be the di-p-tolunesulfonic acid salt of a bis-(L-xcex1-amino acid)-xcex1,xcfx89-alkylene diester; the compound of formula (IV) can be the di-p-tolunesulfonic acid salt of L-lysine benzyl ester; the compound of formula (X) can be 1,3-bis(4-nitro-phenoxycarbonyloxy)propane; or 2,2xe2x80x2-bis-4-nitrophenoxycarbonyloxy ethylether; p/(p+m) can be about 0.9 to about 0.1; and m/(p+m) can be about 0.1 to about 0.9.
The present invention also provides a method for preparing a polymer of formula (XI): 
wherein
is about 0.1 to about 0.9;
p is about 0.9 to about 0.1;
n is about 50 to about 150;
each R2 is independently hydrogen or (C6-C10)aryl(C1-C6)alkyl;
each R3 is independently hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C6-C10)aryl(C1-C6)alkyl;
each R4 is independently (C2-C20)alkylene;
each R5 is independently (C6-C10)aryl optionally substituted with one or more nitro, cyano, halo, trifluoromethyl, or trifluoromethoxy; and
each R6 is independently (C2-C20)alkylene or (C2-C8)alkyloxy(C2-C20)alkylene;
comprising contacting an amount of one or more compounds of formula (III): 
or a suitable salt thereof; and
an amount of one or more compounds of formula (IV): 
or a suitable salt thereof; and
an amount of one or more compounds of formula (X): 
under suitable conditions to provide the polymer of formula (XI).
Specifically, each R2 can independently be hydrogen or benzyl; each R3 can independently be iso-butyl or benzyl; each R4 can independently be (CH2)4, (CH2)6, (CH2)8, or (CH2)12; each R5 can be p-nitrophenyl; each R6 can independently be (CH2)3 or (CH2)2xe2x80x94Oxe2x80x94(CH2)2; the compound of formula (III) can be the di-p-tolunesulfonic acid salt of a bis-(L-xcex1-amino acid)-xcex1,xcfx89-alkylene diester; the compound of formula (IV) can be the di-p-tolunesulfonic acid salt of L-lysine benzyl ester; the compound of formula (X) can be 1,3-bis(4-nitro-phenoxycarbonyloxy)propane, or 2,2xe2x80x2-bis-4-nitrophenoxycarbonyloxy ethylether; p/(p+m) can be about 0.9 to about 0.1; and m/(p+m) can be about 0.1 to about 0.9. The contacting can be carried out in the presence of a base, wherein the base can be triethylamine. The contacting can be carried out in the presence of a solvent, wherein the solvent can be N,N-dimethylacetamide. The contacting can be carried out at a temperature of about 50xc2x0 C. to about 100xc2x0 C. The contacting can occur for about 10 hours to about 24 hours. In addition, the polymer of formula (XI) can optionally be purified.
The biodegradation of the copolyester amides and copolyester urethanes of the present invention allows the delivery of essential xcex1-amino acids to targeted sites (e.g., to facilitate wound repair of injured tissues). In addition, the polymers of the present invention can be used for the attachment free iminoxyl radicals for suppressing inconsolable cell proliferation, and heparin or hirudin for increasing hemocompatibility. These modified polymers can be used to coat stents to suppress restenosis. In addition, the polymers of the present invention can be used as polyacids for the application in gynecology as impregnated contraceptive agents, e.g., for the controlled release of ferrous gluconate and the like. Furthermore, the polymers of the present invention can be used as polyacids for the attachment of unsaturated compounds, e.g., allyl amine or allyl alcohol, to obtain photo-curable and cross-linkable biodegradable polymers. The present polymers can be cross-linked with other polymers containing double bonds to create hybrid materials.
The biological and material properties of the polymers of the present invention can be varied over a wide range because the polymers can be formed from starting materials having varying functional groups (e.g., dicarboxylic acids, diols, and xcex1-amino acids). See, e.g., Examples 1-22. In contrast to conventional poly(xcex1-amino acids), the elastomeric functional copolyester amides and copolyester urethanes of the present invention can be obtained in high yields. See, Table III. For example, the compounds of the present invention can be prepared in yields up to about 97%. In addition, the reaction conditions employed to prepare the polymers of the present invention are relatively simple and the reagents are relatively inexpensive.
The following definitions are used, unless otherwise described: halo can be chloro, fluoro, bromo, or iodo. Alkyl, alkenyl, alkynyl, etc. denote both straight and branched groups; but reference to an individual radical such as xe2x80x9cpropylxe2x80x9d embraces only the straight chain radical, a branched chain isomer such as xe2x80x9cisopropylxe2x80x9d being specifically referred to.
It will be appreciated by those skilled in the art that compounds of the invention having a chiral center may exist in and be isolated in optically active and racemic forms. Some compounds may exhibit polymorphism. It is to be understood that the present invention encompasses any racemic, optically-active, polymorphic, or stereoisomeric form, or mixtures thereof of a compound of the invention, which possess the useful properties described herein, it being well known in the art how to prepare optically active forms (for example, by resolution of the racemic form by recrystallization techniques, by synthesis from optically-active starting materials, by chiral synthesis, or by chromatographic separation using a chiral stationary phase).
Specific and preferred values listed below for radicals, substituents, and ranges, are for illustration only; they do not exclude other defined values or other values within defined ranges for the radicals and substituents
As used herein, xe2x80x9calkylxe2x80x9d is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, and s-pentyl. xe2x80x9cAlkylenexe2x80x9d is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having two open valences and having the specified number of carbon atoms. Examples of alkylene include, but are not limited to, methylene, ethylene, n-propylene, n-butylene, s-butylene, and n-pentylene. xe2x80x9cAlkoxyxe2x80x9d represents an alkyl group as defined above with the indicated number of carbon atoms attached through an oxygen bridge. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy. xe2x80x9cAlkenylxe2x80x9d is intended to include hydrocarbon chains of either a straight or branched configuration having one or more unsaturated carbon-carbon bonds, which may occur in any stable point along the chain, such as ethenyl and propenyl. xe2x80x9cAlkynylxe2x80x9d is intended to include hydrocarbon chains of either a straight or branched configuration having one or more triple carbon-carbon bonds, which may occur in any stable point along the chain, such as ethynyl and propynyl. xe2x80x9cArylxe2x80x9d denotes a phenyl radical or an ortho-fused bicyclic carbocyclic radical having about nine to ten ring atoms in which at least one ring is aromatic. Examples of aryl include, but are not limited to phenyl and naphthyl.
A specific value for R1 is (CH2)4, (CH2)8, or (CH2)12.
A specific value for R2 is hydrogen, benzyl, sec-phenethyl, or methylbenzyl. Another specific value for R2 is benzyl.
A specific value for R3 is iso-butyl or benzyl.
A specific value for R4 is (CH2)4, (CH2)6, (CH2)8, or (CH2)12.
A specific value for R5 is p-nitrophenyl.
A specific value for R6 is (CH2)3 or (CH2)2xe2x80x94Oxe2x80x94(CH2)2.
A specific value for m is about 0.25 to about 0.75.
A specific value for p is about 0.75 to about 0.25.
A specific value for n is about 75 to about 125.
A specific value for p/(p+m) is about 0.75 to about 0.25.
A specific value for m/(p+m) is about 0.25 to about 0.75.
A specific value for (p+m) is about 0.9 to about 1.1. Another specific value for (p+m) is about 0.75 to about 1.25.
A specific group of compounds of formula (III) are the di-p-tolunesulfonic acid salts of a bis-(L-xcex1-amino acid)-xcex1,xcfx89-alkylene diester: 
wherein
each R3 is independently is iso-butyl or benzyl; and
R4 is (CH2)4, (CH2)6, or (CH2)12.
A specific group of compounds of formula (IV) are the di-p-tolunesulfonic acid salts of L-lysine arylalkyl esters: 
wherein
R2 is benzyl sec-phenethyl, or methylbenzyl. More specifically, R2 can be benzyl.
A specific group of compounds of formula (V) are compounds of the formula: 
wherein
R1 is (CH2)4, (CH2)8, or (CH2)12; and
R5 is p-nitrophenyl.
For example, a specific group of compounds of formula (V) are di-p-nitrophenyl adipate, di-p-nitrophenyl sebacinate, and di-p-nitrophenyl dodecyldicarboxylate
A specific group of compounds of formula (X) are compounds of the formula: 
wherein
R5 is p-nitrophenyl; and
R6 is (CH2)3 or (CH2)2xe2x80x94Oxe2x80x94(CH2)2.
For example, a specific group of compounds of formula (X) are 1,3-bis(4-nitro-phenoxycarbonyloxy)propane and 2,2xe2x80x2-bis-4-(nitrophenoxycarbonyloxy)ethylether.
In cases where compounds (e.g., starting materials) are sufficiently basic or acidic to form stable nontoxic acid or base salts, the compounds can exist as the acceptable salt. Examples of acceptable salts are organic acid addition salts formed with acids which form an acceptable anion, for example, tosylate, methanesulfonate, acetate, citrate, malonate, tartarate, succinate, benzoate, ascorbate, xcex1-ketoglutarate, and xcex1-glycerophosplhate. Suitable inorganic salts may also exist, including hydrochloride, sulfate, nitrate, bicarbonate, and carbonate salts.
Acceptable salts may be obtained by using standard procedures that are well known in the art, for example by reacting a sufficiently basic compound such as an amine with a suitable acid affording an acceptable anion. Alkali metal (for example, sodium, potassium or lithium) or alkaline earth metal (for example calcium) salts of carboxylic acids can also be made.
Processes for preparing polymers of the present invention (e.g., polymers of formula (VII) and polymers of formula (XI)) are provided as further embodiments of the invention and are as illustrated by the procedures herein below in which the meanings of the generic radicals are as given above unless otherwise qualified.
A polymer of formula (VII) can include one or more subunits of formula (I) and one or more subunits of formula (II). As such, a polymer of formula (VII) can be prepared from a compound of formula (III), from a compound of formula (IV), and from a compound of formula (V). Specifically, a polymer of formula (VII) can be prepared by contacting a compound of formula (III), a compound of formula (IV), and a compound of formula (V) under suitable conditions to provide a polymer of formula (VII).
The compounds of formula (III), (IV), and (V) can be contacted in the presence of a solvent. Any suitable solvent can be employed. When the compounds of formula (III), (IV), and (V) are contacted in the presence of a solvent, the compounds of formula (III), (IV), and (V) are preferably soluble in the solvent. One exemplary suitable solvent is N,N-dimethylacetamide.
The compounds of formula (III), (IV), and (V) can be contacted in the presence of base. Any suitable base can be employed. When the compounds of formula (III), (IV), and (V) are contacted in the presence of a base, the base will preferably adjust the initial pH of the reaction mixture (i.e., the solution including the compounds of formula (III), (IV), and (V)) above about 7. The base is useful to yield the free amines of the compound of formula (III) and the compound of formula (IV). One exemplary suitable base is triethylamine.
The compounds of formula (III), (IV), and (V) can be contacted for a period of time sufficient to provide the polymer of formula (II). For example, the period of time can be from about 1 hour to about 48 hours, inclusive. Preferably, the period of time can be from about 5 hours to about 30 hours, inclusive. More preferably, the period of time can be from about 10 hours to about 24 hours, inclusive.
The compounds of formula (III), (IV), and (V) can be contacted at a temperature sufficient to provide the polymer of formula (VII). For example, the temperature can be from the freezing point of the liquid reaction mixture (e.g., the solvent, base, and the compounds of formula (III), (IV), and (V)) up to about the reflux temperature of the reaction mixture. Preferably, the temperature can be from about 25xc2x0 C. to about 150xc2x0 C. More preferably, the temperature can be from about 50xc2x0 C. to about 100xc2x0 C.
A polymer of formula (XI) can include one or more subunits of formula (VIII) and one or more subunits of formula (IX). As such, a polymer of formula (XI) can be prepared from a compound of formula (III), from a compound of formula (IV), and from a compound of formula (X). Specifically, a polymer of formula (XI) can be prepared by contacting a compound of formula (III), a compound of formula (IV), and a compound of formula (X) under suitable conditions to provide a polymer of formula (XI).
The compounds of formula (III), (IV), and (X) can be contacted in the presence of a solvent. Any suitable solvent can be employed. When the compounds of formula (III), (IV), and (X) are contacted in the presence of a solvent, the compounds of formula (III), (IV), and (X) are preferably soluble in the solvent. One exemplary suitable solvent is N,N-dimethylacetamide.
The compounds of formula (III), (IV), and (X) can be contacted in the presence of a base. Any suitable base can be employed. When the compounds of formula (III), (IV), and (X) a, contacted in the presence of a base, the base will preferably adjust the initial pH of the reaction mixture (i.e., the solution including the compounds of formula (III), (IV), and (X)) above about 7. The base is useful to yield the free amines of the compound of formula (III) and the compound of formula (IV). One exemplary suitable base is triethylamine.
The compounds of formula (III), (IV), and (X) can be contacted for a period of time sufficient to provide the polymer of formula (VII). For example, the period of time can be from about 1 hour to about 48 hours, inclusive. Preferably, the period of time can be from about 5 hour; to about 30 hours, inclusive. More preferably, the period of time can be from about 10 hours to about 24 hours, inclusive.
The compounds of formula (III), (IV), and (X) can be contacted at a temperature sufficient to provide the polymer of formula (VII). For example, the temperature can be from about the freezing point of the liquid reaction mixture (e.g.,the solvent, base, and the compounds of formula (III), (IV), and (X)) up to about the reflux temperature of the reaction mixture. Preferably, the temperature can be from about 25xc2x0 C. to about 150xc2x0 C. More preferably, the temperature can be from about 50xc2x0 C. to about 100xc2x0 C.